Myelodysplastic syndrome (MDS) in many patients is characterized by peripheral blood cytopenias in the presence of cellular or hypocellular marrow. While a proportion of patients will eventually develop acute leukemia, 40 percent-50 percent of patients die with hemorrhagic or infectious complications. Satisfactory therapy, in the form of hemopoietic stem cell transplantation, is available only to a small proportion of patients. New treatment modalities are needed. Recent studies show increased expression of negative regulators of hemopoiesis such as tumor necrosis factor (TNF)-alpha and a high rate of apoptosis (programmed cell death) in MDS marrow. Preliminary investigations suggest that hemopoiesis can be improved by blocking negative regulatory signals or by eliminating the cellular source of those signals. The applicants propose to 1) conduct a series of clinical trials to determine the efficacy of TNFR:Fc (a soluble TNF receptor), antithymocyte globulin (ATG, an anti-T-cell agent), and flt3-ligand (an early activating cytokine) alone and in combination, in improving peripheral cytopenias and stabilizing hemopoiesis in patients with MDS; 2) to carry out in vitro/ex vivo studies on marrow from patients enrolled in those trials to characterize morphology, immunophenotype, expression of TNF-alpha, Fas and Fas-ligand, as well as cytogenetic abnormalities, before and after therapy and to correlate in vitro/ex vivo parameters with in vivo treatment responses and "quality" of response; 3) to develop additional treatment approaches utilizing new probes and reagents. These studies are expected to generate data that will guide the selection of patients for future specific protocols. Optimization of therapy, in turn, should reduce morbidity and mortality associated with MDS and improve the quality of life of patients with MDS.